Project Summary The Tobacco and Environmental Carcinogenesis Program, which received ?Outstanding? merit in its first CCSG submission in 2010, assembles researchers committed to elucidating how exposures to tobacco and environmental carcinogens cause cancer and how these exposures can be mitigated by risk reduction, intervention, and communication strategies. Exposure to carcinogens represents a major cause of human cancers yet individuals who have the same exposures do not all get cancer in the end-organ. This suggests that significant inter-individual differences exist in cancer susceptibility. Understanding the basis of these differences can lead to precision risk reduction, which represents the translational impact of the Program. The foci of the Program is tobacco related cancers (e.g., lung) and asbestos exposure and mesothelioma, with a developing effort in UV/light exposure and melanoma. Each area provides rich opportunities for inter- Programmatic research. The Program owes its translational and transdisciplinary vision to Co-Leaders Drs. Robert Schnoll, a leader in tobacco control, and Trevor Penning, an expert in environmental carcinogenesis. The scientific aims of the Program are to: 1) Elucidate the pathways underlying exposure risk (e.g., risk factors for tobacco dependence; environmental exposures and risk for mesothelioma and melanoma); 2) Identify the mechanisms linking exposure to disease (e.g., steps in multi-stage carcinogenesis); 3) Evaluate methods for exposure and risk reduction (e.g., tobacco cessation treatments; asbestos remediation; UV light protection); and 4) Test methods of risk communication (e.g., tobacco marketing, regulatory science). Program members collaborate extensively, particularly with the Cancer Control and Cancer Therapeutics Programs, on studies of tobacco use, health communication, and smoking cessation, with the Cancer Therapeutics and Immunobiology Programs on investigations in thoracic oncology and immunotherapies, and with the Melanoma and Cutaneous Malignancies Program on UV/light issues. Seminal contributions during the project period include validating the first genetically-informed biomarker for personalized smoking cessation treatment and identifying novel mechanisms by which multi-organ carcinogens (e.g., polycyclic aromatic hydrocarbons) in tobacco smoke and the environment are metabolically activated. The intra- and inter-Programmatic environment is facilitated by active mentoring, symposia, working groups, and pilot grants. The 15 members, who are from five departments and two schools, have $5.9M in external funding (annual direct costs); $5.8M is peer-reviewed and $2.6M is NCI-funded. Collaborative grants include an NCI P50 Tobacco Center of Regulatory Science (with Cancer Control), a P30 Center of Excellence in Environmental Toxicology (CEET; with Cancer Control), a Pharmacogenomics Research Network U01 (with Cancer Control), and an NIH P42 Superfund Research Program on asbestos. Members authored 263 cancer-related publications (21% intra-Programmatic; 30% inter-Programmatic; 46% multi-institutional) during the project period.